Neuropathic pain is a serious clinical issue, and its treatment remains a challenge in contemporary medicine. Thus, dynamic development in the area of animal and clinical studies has been observed. The mechanisms of
neuropathic pain are still not fully understood; therefore, studies investigating these mechanisms are extremely important. However, much evidence indicates that changes in the activation and infiltration of immune cells cause the release of pronociceptive
cytokines and contribute to
neuropathic pain development and maintenance. Moreover, these changes are associated with low efficacy of
opioids used to treat neuropathy. To date, the role of
CC chemokine receptor type 3 (CCR3) in nociception has not been studied. Similarly, little is known about its endogenous
ligands (C-C motif
ligand; CCL), namely, CCL5, CCL7, CCL11, CCL24, CCL26, and CCL28. Our research showed that the development of
hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with upregulation of CCL7 and CCL11 in the spinal cord and dorsal root ganglia (DRG). Moreover, our results provide the first evidence that single and repeated intrathecal administration of the CCR3 antagonist
SB328437 diminishes mechanical and thermal
hypersensitivity. Additionally, repeated administration enhances the
analgesic properties of
morphine and
buprenorphine following nerve injury. Simultaneously, the injection of
SB328437 reduces the
protein levels of some pronociceptive
cytokines, such as
IL-6, CCL7, and CCL11, in parallel with a reduction in the activation and influx of GFAP-, CD4- and MPO-positive cells in the spinal cord and/or DRG. Moreover, we have shown for the first time that an inhibitor of myeloperoxidase-4-aminobenzoic
hydrazide may relieve
pain and simultaneously enhance
morphine and
buprenorphine efficacy. The obtained results indicate the important role of CCR3 and its modulation in
neuropathic pain treatment and suggest that it represents an interesting target for future investigations.